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Stapled α−helical peptide drug development: A potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy
Open accessAbstract
Significance: Stapled α−helical peptides have emerged as a promising new modality for a wide range of therapeutic targets. Here, we describe the development of a stapled α−helical peptide lead molecule for the treatment of cancers that possess the intact p53 tumor suppressor protein but are resistant to drug therapy because of the overexpression of inhibitory proteins MDM2 and MDMX. The molecule ATSP-7041 is a highly potent dual inhibitor of both MDM2 and MDMX that is shown to effectively reactivate the p53 tumor suppressor pathway in a mechanism-dependent manner in p53-positive cancers in vitro and in vivo.
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Therapeutic Peptides: Current Applications and Future Directions
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Small-Molecule Inhibitors of Protein-Protein Interactions: Progressing toward the Reality
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Metadata
- Authors
- Chang, Y. S., Graves, B., Guerlavais, V., Tovar, C., Packman, K., To, K.-H., Olson, K. A., Kesavan, K., Gangurde, P., Mukherjee, A., Baker, T., Darlak, K., Elkin, C., Filipovic, Z., Qureshi, F. Z., Cai, H., Berry, P., Feyfant, E., Shi, X. E., Horstick, J., Annis, D. A., Manning, A. M., Fotouhi, N., Nash, H., Vassilev, L. T., & Sawyer, T. K.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2013-08-14
- Volume
- 110
- Issue
- 36
- Pages
- E3445-54
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2072435450
- Cited by
- 660
- References
- 19
- FWCI
- 21.79
- Type
- journal article
- Language
- en
- Open access
- green
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- Chang, Y. S., Graves, B., Guerlavais, V., Tovar, C., Packman, K., To, K.-H., Olson, K. A., Kesavan, K., Gangurde, P., Mukherjee, A., Baker, T., Darlak, K., Elkin, C., Filipovic, Z., Qureshi, F. Z., Cai, H., Berry, P., Feyfant, E., Shi, X. E., . . . Sawyer, T. K. (2013). Stapled α−helical peptide drug development: A potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1303002110
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
